Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial.

BACKGROUND: Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. METHODS: In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. RESULTS: Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30-133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14-1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01-0.89 and aOR 0.09; 95% CI 0.01-0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO2 ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01-0.90, and aOR 0.09; 95% CI 0.03-0.27, respectively). CONCLUSIONS: Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

Does awake prone positioning prevent the use of mechanical respiratory support or death in COVID-19 patients on standard oxygen therapy hospitalised in general wards? A multicentre randomised controlled trial: the PROVID-19 protocol.

INTRODUCTION: COVID-19 is responsible of severe hypoxaemia and acute respiratory distress syndrome (ARDS). Prone positioning improves oxygenation and survival in sedated mechanically patients with ARDS not related to COVID-19. Awake prone positioning is a simple and safe technique which improves oxygenation in non-intubated COVID-19 patients. We hypothesised that early prone positioning in COVID-19 patients breathing spontaneously in medical wards could decrease the rates of intubation or need for noninvasive ventilation or death. METHODS AND ANALYSIS: PROVID-19 is an investigator-initiated, prospective, multicentre randomised, controlled, superiority trial comparing awake prone positioning to standard of care in hypoxaemic COVID-19 patients in 20 medical wards in France and Monaco. Patients are randomised to receive either awake prone position plus usual care or usual care alone with stratification on centres, body mass index and severity of hypoxaemia.The study objective is to compare the rate of treatment failure defined as a composite endpoint comprising the need for non-invasive ventilation (at two pressure levels) or for intubation or death, between the intervention group (awake prone position plus usual care) and the usual care (usual care alone) group at 28 days. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the ethics committees (Comité de protection des personnes Ouest VI, France, no 1279 HPS2 and Comité Consultatif d'Ethique en matière de Recherche Biomédicale, Monaco, no 2020.8894 AP/jv), and patients are included after written informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04363463.

Real-world Risk of Relapse of Giant Cell Arteritis Treated With Tocilizumab: A Retrospective Analysis of 43 Patients.

OBJECTIVE: Tocilizumab (TCZ), an interleukin 6 (IL-6) receptor antagonist, is approved for giant cell arteritis (GCA) as a cortisone-sparing strategy and in refractory patients. This study assessed the real-world efficacy, safety, and long-term outcomes of patients with GCA treated with TCZ. METHODS: We conducted a multicenter retrospective observational study at 3 French centers. All patients aged ≥ 50 years who met the American College of Rheumatology (ACR) criteria, and had received at least 1 dose of TCZ were included. Relapse was defined by therapeutic escalation, such as increased doses of corticosteroids (CS), resumption of CS after weaning, or introduction or intensification of adjuvant therapy. RESULTS: Between 2013 and 2019, 43 patients were included. Patients were followed up for a median 511 days between GCA diagnosis and inclusion, with 34/43 (79%) patients experiencing relapses. At inclusion, median age was 77 years, and median dose of CS was 15 mg/day. After inclusion, the mean cumulative dose of CS was 2.1 g/year vs 9.4 g/year before inclusion (P < 2 × 10-7), with 12/43 (28%) patients experiencing relapses on TCZ. Among 29 patients undergoing TCZ discontinuation, 18 (62%) experienced relapses. Factors associated with relapse after inclusion were introduction of TCZ > 6 months after diagnosis (P = 0.005), absence of ischemic signs at diagnosis (P = 0.006), relapse rate > 0.8/year (P = 0.03), and absence of CS tapering ≤ 5 mg/day (P = 0.03) before inclusion. Serious adverse events occurred in 18/43 patients (42%), including 4 deaths. CONCLUSION: Our results confirm the effectiveness of TCZ for CS sparing, but after discontinuation of treatment, TCZ allows for a prolonged remission in < 50% of patients. Attention must be paid to the tolerance of this long-term treatment in this elderly, heavily treated refractory population.